DESCRIPTION: (Applicant's Abstract) The long-term objective of this proposal is to establish clonal lines of dopamine (DA)-producing nerve cells in vitro in order to evaluate their efficacy in improving the symptoms of Parkinson's disease (PD). We have established clonal lines of rat immortalized DA-producing nerve cells in vitro and can generate 100 percent terminally differentiated neuroblastoma (NB) cells. The immortalized cells when transplanted into the striatum of rats with 6- hydroxydopamine (6-OHDA) lesions, survived, did not produce tumors and reduced amphetamine-induced circling after 30 days of grafting, whereas the differentiated NB cells were ineffective in producing such an effect. The specific aims of this renewal application are as follows: a) to determine the long-term efficacy of grafted immortalized rat DA- producing nerve cells in improving the neurological deficits of rats with 6-OHDA lesions; b) to establish and characterize human immortalized DA-producing nerve cells in vitro, and then test their efficacy in improving neurological deficits of rats with 6-OHDA lesions; c) to establish hybrid cells by fusing DA-producing immortalized nerve cells with glia cells, characterize them, and then test their efficacy in improving neurological deficits of rats with 6-OHDA lesions; and d) to study the induction of morphological and biochemical differentiated functions in parent and hybrid dopamine-producing cells in vitro, and then test their efficacy for improving neurological deficits in rats with 6-OHDA lesions. Future studies will focus on testing the efficacy of immortalized DA-producing nerve cells first in MPTP-treated monkeys with the ultimate goal of eventually treating patients with advanced Parkinson's disease.